Project Summary/Abstract We propose to investigate the association between suicidal cognition and opioid overdose in adults with opioid use disorder. In 2016, over 42,000 people died from opioid overdose in the United States, continuing the escalation of deaths since the late 1990s. Moreover, up to 70% of those with opioid use disorder report a history of nonfatal overdose, which is associated with costly health care service utilization and risk for future fatal overdose. Overdoses are generally categorized as either intentional (i.e., suicidal) or accidental. Data suggest that accidental overdose and suicide are related and often co-occur among those with opioid use disorder. An estimated 20-30% of those with opioid use disorder report a history of both suicide attempt and overdose. Furthermore, suicide attempts and overdoses are often preceded by a stressful event, suggesting that stress may be a common precipitating factor for both overdose and suicide. However, the relationship between suicidal thoughts and opioid overdose may be greatly underestimated. Dichotomous classification schemes for overdose are highly vulnerable to misclassification because (1) suicidal thoughts occur along a continuum, and (2) suicide assessment is subject to well-known reporting biases (e.g., reluctance of participants to report suicidal thoughts due to fear of hospitalization). Thus, many overdoses classified as accidental may in fact be preceded by thoughts of death, a finding supported by our preliminary data. Moreover, the use of implicit measurement of suicidal cognition affords significant additive benefits beyond the use of self-report measures alone, and may detect suicidal thoughts that are missed using other methods. Accordingly, there is an urgent need to quantify the association between suicidal thoughts and opioid overdose to enhance understanding of the impact of suicide on the overdose crisis and to identify potential targets for intervention. Therefore, our objective is to investigate the association between suicidal cognition and opioid overdose and to quantify the association between heightened reactivity to stress and both overdose and suicide attempts. The proposed study consists of two aims for which we propose to recruit men and women with opioid use disorder with and without a history of opioid overdose. The first aim is to quantify the association between implicit and explicit suicidal cognition and opioid overdose. The second aim is to quantify the association between heightened affective and peripheral physiological reactivity to stress and history of overdose and suicide attempts. The results from this study will provide important information about the overlap between suicidal thoughts and opioid overdose, and the relationship between reactivity to stress and these two potentially fatal behaviors. The results of this study will critically advance knowledge on the link between suicide and opioid overdose and ultimately inform the development of novel treatments to reduce the risk for overdose.